TLR7/8 激动剂是多功能免疫刺激剂，能够治疗病毒感染、自身免疫和癌症等多种疾病。尽管 TLR7/8 的结构相似，但它们的免疫刺激机制和时程反应显着不同。在本研究中，利用经济的结构单元 2,6-二氯嘌呤合成了一系列新的 TLR7 选择性激动剂。化合物 27b 对 hTLR7 显示出最有效的活性，EC50 为 17.53 nM，并表现出高 hTLR7 选择性（针对 TLR8 的 224 倍）。 27b有效刺激小鼠巨噬细胞分泌促炎细胞因子，增强鼻内疫苗体内针对甲型流感病毒的功效。体液和粘膜抗体滴度评估证实，27b 可以提高 IgG 和 IgA 水平，从而防止同源和异源流感病毒感染。这些发现表明，27b 是一种很有前途的候选药物，可作为预防病毒感染的疫苗佐剂，或作为具有长期活性的强效免疫调节剂来治疗免疫抑制疾病。

TLR7/8 agonists are versatile immune stimulators capable of treating various diseases such as viral infections, autoimmune, and cancer. Despite the structural similarity of TLR7/8, their immune stimulation mechanisms and time-course responses significantly differ. In this study, a new series of TLR7-selective agonists was synthesized utilizing the economical building block 2,6-dichloropurine. Compound 27b showed the most potent activity on hTLR7 with an EC50 of 17.53 nM and demonstrated high hTLR7 selectivity (224 folds against TLR8). 27b effectively stimulated the secretion of proinflammatory cytokines in mouse macrophages and enhanced intranasal vaccine efficacy against influenza A virus in vivo. Assessment of humoral and mucosal antibody titers confirmed that 27b elevates IgG and IgA levels, protecting against both homologous and heterologous influenza viral infections. These findings suggest that 27b is a promising candidate as a vaccine adjuvant to prevent viral infections or as a robust immunomodulator with prolonged activity for treating immune-suppressed diseases.